A number of unique Research Reagents have been derived in the Drucker laboratory for analysis of glucagon gene expression and the biology of glucagon-like peptide action.
A differentiated mouse intestinal endocrine cell line, GLUTag cells, that secretes GLP-1 and GLP-2 in a regulated manner, permitting the analysis of the factors that regulate glucagon-like peptide synthesis and secretion
Derivatized GLUTag cells are being created that permit analysis of both glucagon gene transcription and peptide secretion through rapid screening methodologies
Antisera to both GLP-1, GLP-2 and the GLP-1 receptor
The laboratory has isolated and characterized both rat and human proglucagon genes and cDNAs
Transgenic mice that express a growth hormone reporter gene under the control of a human glucagon gene promoter in the enteroendocrine cells of the small and large intestine. These mice .Divergent regulation of human and rat proglucagon gene promoters in vivo. 1999 Am J Physiol 277:G829-37) provide a unique opportunity to analyze the control of human GLP-1 and GLP-2 biosynthesis and secretion in non-transformed cell types in vivo.
Glucagon-like peptide-1 receptor knockout mice have been developed that contain a null mutation in the GLP-1 receptor gene. These mice exhibit mild diabetes and provide a useful model for analyzing the importance of GLP-1 receptor-mediated signaling during development and in adult mouse physiology
Humanized GLP-1R mice that express the human GLP-1R under the control of the pdx1 promoter in the Glp1r-/- mouse background have also been generated and functionally restore human GLP-1R expression and activity in Glp1r-/- islets. Pancreatic GLP-1 receptor activation is sufficient for GLP-1R-dependent control of glucose homeostasis in mice J Clin Invest 2011 doi:10.1172/JCI42497
Transgenic mice that over-express exendin-4 under the control of a mouse metallothionein promoter have been generated and provide a unique model for the study of exendin-4 safety and efficacy in vivo. Sustained expression of exendin-4 does not perturb glucose homeostasis, β cell mass or food intake in metallothionein-preproexendin transgenic mice J. Biol. Chem. 2000 275: 34471-34477